Method Of Making Particles For Use In A Pharmaceutical Composition

Abstract

A method for making composite excipient particles for use in a pharmaceutical composition comprises a milling step in which particles of an excipient material are milled in the presence of an additive material. The product particles are of small size and the milling requires relatively low input of time and energy. The composite particles are suitable for use in inhalable pharmaceutical compositions.

1 . A method for making composite excipient particles for use in a pharmaceutical composition, the method comprising a milling step in which particles of an excipient material are milled in the presence of an additive material. 
     
     
         2 . The method of  claim 1 , in which particles of the excipient material comprise a mass median aerodynamic diameter (MMAD) that is substantially reduced during the milling step. 
     
     
         3 . The method of  claim 2 , in which the mass median aerodynamic diameter of particles of the excipient material is reduced by at least 50% during the milling step. 
     
     
         4 . The method of  claim 2 , in which, after the milling step, the mass median aerodynamic diameter of the composite excipient particles is not more than 50 μm. 
     
     
         5 . The method of  claim 1 , in which the milling step is carried out in the presence of a liquid. 
     
     
         6 . The method of  claim 5 , which further comprises the step of removing the liquid after the milling step. 
     
     
         7 . The method of  claim 6 , in which the liquid is removed by spray drying. 
     
     
         8 . The method of  claim 1 , further comprising, after the milling step, an agglomeration step in which the composite excipient particles are agglomerated to form agglomerated particles. 
     
     
         9 . The method of  claim 8 , in which the agglomeration step is a spray drying step. 
     
     
         10 . The method of  claim 1 , wherein the excipient material is a crystalline sugar. 
     
     
         11 . The method of  claim 1 , in which the additive material comprises an amino acid. 
     
     
         12 . The method of  claim 1 , in which the additive material comprises a phospholipid. 
     
     
         13 . The method of  claim 1 , in which the additive material comprises a metal stearate. 
     
     
         14 . Composite excipient particles for use in a pharmaceutical composition as made by the method of  claim 1 . 
     
     
         15 . A pharmaceutical composition comprising composite excipient particles, each composite excipient particle comprising a particle of an excipient material and an additive material on the surface of that particle of excipient material, the composite excipient particles having a mass median aerodynamic diameter of less than 20 μm. 
     
     
         16 . The pharmaceutical composition of  claim 15  further comprising active particles. 
     
     
         17 . The pharmaceutical composition of  claim 16  which is a dry powder and is suitable for use in a dry powder inhaler. 
     
     
         18 . The pharmaceutical composition of  claim 17  further comprising carrier particles. 
     
     
         19 . The pharmaceutical composition of  claim 18  wherein the composite excipient particles are in an amount of 1 to 40% based on the weight of the carrier particles. 
     
     
         20 . The pharmaceutical composition of  claim 18 , in which the carrier particles have a fissured surface. 
     
     
         21 . The pharmaceutical composition of  claim 18 , in which the carrier particles are of a crystalline sugar having a tapped density not exceeding 0.75 g/cm3. 
     
     
         22 . The pharmaceutical composition of  claim 18 , in which the carrier particles have a bulk density as measured by mercury intusion porosimetry of not exceeding 0.6 g/cm3. 
     
     
         23 . The pharmaceutical composition of  claim 18 , in which the carrier particles have a MMAD of at least 175 μm. 
     
     
         24 . The pharmaceutical composition of  claim 16  further comprising a propellant and is suitable for use in a pressurized metered dose inhaler. 
     
     
         25 . A dry powder for use in a dry powder inhaler comprising active particles, carrier particles for carrying the active particles, and composite excipient particles, wherein each of the composite excipient particles comprise a particle of excipient material having an additive material on the surface of that particle of excipient material, the additive material being suitable for the promotion of the release of the active particles from the carrier particles on actuation of the inhaler. 
     
     
         26 . A method for making particles of an excipient material comprising the step of using an additive material as a milling aid in the milling of particles of the excipient material.